Richards R I, Kondo I, Holman K, Yamauchi M, Seki N, Kishi K, Staples A, Sutherland G R, Hori T
Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, Australia.
Am J Med Genet. 1994 Jul 15;51(4):412-6. doi: 10.1002/ajmg.1320510422.
Fragile X syndrome, one of the most common human genetic diseases, is characterized by a unique genetic mechanism which involves dynamic mutation in a heritable unstable DNA sequence, a p(CCG)n repeat, in the FRAXA locus. It has recently been suggested that a few founder chromosomes are responsible for most fragile X mutations in the Caucasian population. In order to investigate the origin of the fragile X mutations in the Japanese population, we analyzed haplotypes of the FRAXA locus in 40 unrelated fragile X chromosomes and 142 normal X chromosomes in Japanese males, by using two polymorphic AC repeats, FRAXAC1 and FRAXAC2, which flank the fragile site. This analysis provided evidence for founder fragile X chromosomes in the Japanese population, similar to that in Caucasians, although different haplotypes are involved. The distribution of normal allele size of the p(CCG)n repeat among the X chromosomes in the Japanese population is very similar to that reported for Caucasians, except that the most frequent copy number (n = 28) is one copy less than that in Caucasians and that there is an additional peak at 35 copies. There is significant correlation between FRAXAC alleles and the p(CCG)n repeat copy number in non-fragile X chromosomes, however, alleles with more than 31 copies of the p(CCG)n repeat do not segregate with either of the fragile X common FRAXAC haplotypes.
脆性X综合征是最常见的人类遗传疾病之一，其特征是一种独特的遗传机制，该机制涉及FRAXA位点上一个可遗传的不稳定DNA序列p(CCG)n重复序列中的动态突变。最近有人提出，少数奠基者染色体导致了白种人群中大多数脆性X突变。为了研究日本人群中脆性X突变的起源，我们通过使用位于脆性位点两侧的两个多态性AC重复序列FRAXAC1和FRAXAC2，分析了40条无关的脆性X染色体和142条日本男性正常X染色体上FRAXA位点的单倍型。该分析为日本人群中存在奠基者脆性X染色体提供了证据，这与白种人群相似，尽管涉及不同的单倍型。日本人群X染色体中p(CCG)n重复序列正常等位基因大小的分布与报道的白种人群非常相似，只是最常见的拷贝数（n = 28）比白种人群少一个拷贝，并且在35拷贝处有一个额外的峰值。在非脆性X染色体中，FRAXAC等位基因与p(CCG)n重复序列拷贝数之间存在显著相关性，然而，p(CCG)n重复序列拷贝数超过31的等位基因并不与任何一种常见的脆性X FRAXAC单倍型分离。
